PROJECT SUMMARY/ABSTRACT Macrophages commonly account for a significant mass fraction of tumors of various cancers and are derived from circulating monocytes. While the monocytes can differentiate into either tumoricidal M1 macrophages or pro-tumor M2 macrophages, macrophages in the tumors are typically M2 polarized. Our long-term goal is to develop a novel therapy for treating metastatic cancers through increasing the population of M1 macrophages while decreasing the population of M2 macrophages in the metastatic tumors. The overall objective of this application is to prove the concept of this therapy in vitro and consequently lay a foundation for its further development by in vivo studies. Our specific aims are to establish a protocol for preparing microdevice-monocyte complexes with desirable properties and develop a microdevice formulation that allows effective killing of cancer cells. This work is innovative in that microdevices are used for the first time to endow monocytes with an ability to target cancer cells and promote the monocytes to differentiate into M1 macrophages.